Scientists locate neurons involved in fear reduction in long-term trauma

Researchers from Ecole Polytechnique Federale de Lausanne (EPFL) have for the first time located the cells that help reprogram long-lasting memories of trauma towards safety.

The study shows at the cellular level how therapy can treat such long-term memories of trauma.

Researchers have long been debating whether reduced fear results when the original memory of fear is suppressed by a new memory of safety or whether the original fear is rewritten towards safety.

Although the current findings don’t exclude suppression, they demonstrate for the first time the importance of rewriting in treating traumatic memories.

As reported in the journal Science, the researchers found that a reduction in long-lasting trauma (remote fear) is connected to the activity of the same group of neurons that are involved in storing the memories in the first place.

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Working with mice, professor Johannes Gräff and colleagues located the neurons in an area of the hippocampus called the dentate gyrus, which is involved in the encoding, recall and reduction of fear.

The mice were genetically engineered to carry a “reporter” gene that emits a measurable signal following neuronal activity and were subjected to a fear-training exercise that produces long-term traumatic memories.

The team first identified the group of neurons in the dentate gyrus that are involved in storing the traumatic memories. Next, the mice were subjected to fear reduction training, which is similar to the exposure-based therapy used to treat humans.

When the researchers next looked at the animals’ brains, they found that some of the neurons active when recalling the memories were still active once the animals were no longer demonstrating fear. Importantly, the less fear the mice showed, the more cells were reactivated. This suggested that the same neurons involved in storing the memories are also involved in attenuating them.

The team then reduced the excitability of the recall neurons during the fear reduction training and found that the mice had less fear reduction than control mice. However, no such effect was observed when they increased the excitability of other neurons present in the dentate gyrus, suggesting that it is the recall neurons that are essential for fear reduction.

Furthermore, when the researchers increased the excitability of the recall neurons during therapy, the mice showed improved fear reduction.

Gräff and colleagues therefore conclude that the reduction of remote fear is dependent on the continued activity of the recall neurons they located in the dentate gyrus.

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